Cross-sectional and Longitudinal Analysis of the Relationship Between Aβ Deposition, Cortical Thickness, and Memory in Cognitively Unimpaired Individuals and in Alzheimer Disease

Doré, Vincent; Villemagne, Victor L.; Bourgeat, Pierrick; Fripp, Jürgen; Acosta, Oscar; Chételat, Gaël; Zhou, Luping; Martins, Ralph N.; Ellis, Kathryn A.; Masters, Colin L.; Ames, David; Salvado, Olivier; Rowe, Christopher C.

doi:10.1001/jamaneurol.2013.1062

Cited by 175 publications

(137 citation statements)

References 48 publications

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“…Despite the small sample size and a cross-sectional design, the findings are consistent with the current study that there is an association between higher PiB retention at baseline and increased rates of cortical atrophy. Several longitudinal studies in non-demented older adults also support our finding that higher PiB retention at baseline is associated with greater atrophy rates (Chetelat et al, 2012;Andrews et al, 2013;Dore et al, 2013;Araque Caballero et al, 2015;Petersen et al, 2016).…”

Section: Discussionsupporting

confidence: 86%

Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies

Sarro¹,

Senjem

Lundt

et al. 2016

Brain

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Alzheimer's disease pathology frequently coexists with Lewy body disease at autopsy in patients with probable dementia with Lewy bodies. More than half of patients with probable dementia with Lewy bodies have high amyloid-b deposition as measured with 11 C-Pittsburgh compound B binding on positron emission tomography. Biomarkers of amyloid-b deposition precede neurodegeneration on magnetic resonance imaging during the progression of Alzheimer's disease, but little is known about how amyloid-b deposition relates to longitudinal progression of atrophy in patients with probable dementia with Lewy bodies. We investigated the associations between baseline 11 C-Pittsburgh compound B binding on positron emission tomography and the longitudinal rates of grey matter atrophy in a cohort of clinically diagnosed patients with dementia with Lewy bodies (n = 20), who were consecutively recruited to the Mayo Clinic Alzheimer's Disease Research Centre. All patients underwent 11 C-Pittsburgh compound B positron emission tomography and magnetic resonance imaging examinations at baseline. Follow-up magnetic resonance imaging was performed after a mean (standard deviation) interval of 2.5 (1.1) years. Regional grey matter loss was determined on threedimensional T 1 -weighted magnetic resonance imaging with the tensor-based morphometry-symmetric normalization technique. Linear regression was performed between baseline 11 C-Pittsburgh compound B standard unit value ratio and longitudinal change in regional grey matter volumes from an in-house modified atlas. We identified significant associations between greater baseline 11 C-Pittsburgh compound B standard unit value ratio and greater grey matter loss over time in the posterior cingulate gyrus, lateral and medial temporal lobe, and occipital lobe as well as caudate and putamen nuclei, after adjusting for age (P 5 0.05). Greater baseline 11 C-Pittsburgh compound B standard unit value ratio was also associated with greater ventricular expansion rates (P 5 0.01) and greater worsening over time in Clinical Dementia Rating Scale, sum of boxes (P = 0.02). In conclusion, in patients with probable dementia with Lewy bodies, higher amyloid-b deposition at baseline is predictive of faster neurodegeneration in the cortex and also in the striatum. This distribution is suggestive of possible interactions among amyloid-b, tau and a-synuclein aggregates, which needs further investigation. Furthermore, higher amyloid-b deposition at baseline predicts a faster clinical decline over time in patients with probable dementia with Lewy bodies. Keywords: DLB; structural MRI; beta-amyloid; amyloid imaging; brain atrophy Abbreviations: AChEI = acetylcholinesterase inhibitor; CDR-SOB = Clinical Dementia Rating scale, Sum of Boxes; DLB = dementia with Lewy bodies; MMSE = Mini-Mental State Examination; PiB = 11 C-Pittsburgh compound B; SUVR = standardized uptake value ratio; TBM-SyN = tensor-based morphometry using symmetric diffeomorphic image normalization; UPDRS-III =

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Section: Discussionsupporting

confidence: 86%

Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies

Sarro¹,

Senjem

Lundt

et al. 2016

Brain

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“…The observed Ab-induced alteration in the entorhinal cortex-detected in both global Ab analyses and colocalized PiB/MRI analyses-is consistent with other studies revealing the loss of cortical mass in the entorhinal region, as a result of amyloid aggregation in the elderly [11,31]. The entorhinal cortex, which is a key afferent to the hippocampus, has been evidenced as a crucial center of AD pathology and one of the earliest areas to demonstrate degeneration [32].…”

Section: Discussionsupporting

confidence: 89%

“…For example, in a study of older cognitively normal (CN) individuals, Becker and colleagues [10] found that Ab deposition is associated with regional cortical thinning especially in posteromedial and lateral parietal structures. Similarly, Dor e and colleagues [11] found that an increase in Ab accumulation was associated with decreased cortical thickness in the posterior cingulate, precuneus, and hippocampus among CN individuals. Other studies using cerebrospinal fluid (CSF) biomarkers for Ab have found similar associations between Ab aggregation and structural brain changes in ADsusceptible regions [12].…”

Section: Introductionmentioning

confidence: 81%

Ic‐p‐118: Amyloid Burden, Cortical Thickness, and Cognitive Function in the Wisconsin Registry for Alzheimer's Prevention

Doherty

Oh²,

Schultz

et al. 2014

Alzheimer's & Dementia

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There is a growing interest in understanding how amyloid b (Ab) accumulation in preclinical Alzheimer's disease relates to brain morphometric measures and cognition. Existing investigations in this area have been primarily conducted in older cognitively normal (CN) individuals. Therefore, not much is known about the associations between Ab burden, cortical thickness, and cognition in midlife. We examined this question in 109, CN, late to middle-aged adults (mean age 5 60.72 6 5.65 years) from the Wisconsin Registry for Alzheimer's Prevention. They underwent Pittsburgh Compound B (PiB) and anatomical magnetic resonance (MR) imaging, and a comprehensive cognitive examination. Blinded visual rating of the PiB scans was used to classify the participants as Ab1 or Ab2. Cortical thickness measurements were derived from the MR images. The Ab1 group exhibited significant thinning of the entorhinal cortex and accelerated age-associated thinning of the parahippocampal gyrus compared with the Ab2 group. The Ab1 group also had numerically lower, but nonsignificant, test scores on all cognitive measures, and significantly faster age-associated cognitive decline on measures of Speed & Flexibility, Verbal Ability, and Visuospatial Ability. Our findings suggest that early Ab aggregation is associated with deleterious changes in brain structure and cognitive function, even in midlife, and that the temporal lag between Ab deposition and the inception of neurodegenerative/cognitive changes might be narrower than currently thought.

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“…In contrast to BDNF, GWAS of Alzheimer's disease identify carriage of APOE "4 as increasing risk for Alzheimer's disease (Lambert et al, 2013). We have also reported that in preclinical sporadic Alzheimer's disease, the APOE "4 allele increases the rate of memory decline and brain volume loss associated with high amyloid-b (Dore et al, 2013;Lim et al, 2014aLim et al, , 2015c. We have also observed that amyloid-b + older adults who carry both the APOE "4 and BDNF Met 66 allele show greater memory decline than those who carry either one by itself (Lim et al, 2015b).…”

Section: Discussionmentioning

confidence: 93%

BDNFVal66Met moderates memory impairment, hippocampal function and tau in preclinical autosomal dominant Alzheimer’s disease

Lim

Hassenstab

Cruchaga

et al. 2016

Brain

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) for a scientific commentary on this article. The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is implicated in synaptic excitation and neuronal integrity, and has previously been shown to moderate amyloid-b-related memory decline and hippocampal atrophy in preclinical sporadic Alzheimer's disease. However, the effect of BDNF in autosomal dominant Alzheimer's disease is unknown. We aimed to determine the effect of BDNF Val66Met on cognitive function, hippocampal function, tau and amyloid-b in preclinical autosomal dominant Alzheimer's disease. We explored effects of apolipoprotein E (APOE) "4 on these relationships. The Dominantly Inherited Alzheimer Network conducted clinical, neuropsychological, genetic, biomarker and neuroimaging measures at baseline in 131 mutation noncarriers and 143 preclinical autosomal dominant Alzheimer's disease mutation carriers on average 12 years before clinical symptom onset. BDNF genotype data were obtained for mutation carriers (95 Val 66 homozygotes, 48 Met 66 carriers). Among preclinical mutation carriers, Met 66 carriers had worse memory performance, lower hippocampal glucose metabolism and increased levels of cerebrospinal fluid tau and phosphorylated tau (p-tau) than Val 66 homozygotes. Cortical amyloid-b and cerebrospinal fluid amyloidb 42 levels were significantly different from non-carriers but did not differ between preclinical mutation carrier Val 66 homozygotes and Met 66 carriers. There was an effect of APOE on amyloid-b levels, but not cognitive function, glucose metabolism or tau. As in sporadic Alzheimer's disease, the deleterious effects of amyloid-b on memory, hippocampal function, and tau in preclinical autosomal dominant Alzheimer's disease mutation carriers are greater in Met 66 carriers. To date, this is the only genetic factor found to moderate downstream effects of amyloid-b in autosomal dominant Alzheimer's disease.

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Cross-sectional and Longitudinal Analysis of the Relationship Between Aβ Deposition, Cortical Thickness, and Memory in Cognitively Unimpaired Individuals and in Alzheimer Disease

Cited by 175 publications

References 48 publications

Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies

Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies

Ic‐p‐118: Amyloid Burden, Cortical Thickness, and Cognitive Function in the Wisconsin Registry for Alzheimer's Prevention

BDNFVal66Met moderates memory impairment, hippocampal function and tau in preclinical autosomal dominant Alzheimer’s disease

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